Circular RNA circ_0001017 Sensitizes Cisplatin-Resistant Gastric Cancer Cells to Chemotherapy by the miR-543/PHLPP2 Axis

Resistance to cisplatin (CDDP) remains a major challenge for the treatment of gastric cancer (GC). Circular RNAs (circRNAs) have been implicated in the development of CDDP resistance of GC. However, the precise actions of circ_0001017 in CDDP resistance of GC remain to be elucidated. The levels of circ_0001017, microRNA (miR)-543 and PH-domain and leucine-rich repeat protein phosphatase 2 (PHLPP2) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot was used to analyze the protein levels of Vimentin, N-cadherin, E-cadherin, and PHLPP2. Ribonuclease R (RNase R) assay was applied to evaluate the stability of circ_0001017. Cell viability and proliferation, colony formation ability, cell cycle distribution and apoptosis, and migration and invasion were detected by the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays, respectively. Direct relationship between miR-543 and circ_0001017 or PHLPP2 was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model assay was used to assess the function of circ_0001017 in vivo. Low expression of circ_0001017 was associated with CDDP resistance of GC. Enforced expression of circ_0001017 impeded growth, metastasis, and enhanced apoptosis of HGC-27/R and AGS/R cells and sensitized them to CDDP in vitro. Circ_0001017 targeted miR-543, and circ_0001017 regulated CDDP-resistant cell behaviors and CDDP sensitivity by suppressing miR-543. PHLPP2 was a direct target of miR-543, and circ_0001017 controlled PHLPP2 expression through miR-543. Moreover, miR-543 knockdown-mediated promotion of PHLPP2 impacted CDDP-resistant cell behaviors and CDDP sensitivity in vitro. Additionally, elevated expression of circ_0001017 hindered growth of HGC-27/R cells and sensitized them to CDDP in vivo. Our findings demonstrated that enforced expression of circ_0001017 suppressed malignant behaviors and enhanced CDDP sensitivity of CDDP-resistant GC cells at least partially by the miR-543/PHLPP2 axis.